Project Summary This competing renewal application proposes to extend and enhance our work aimed at understanding how social status fosters obesity and insulin resistance in adolescence and early adulthood. Disentangling how domains of social disadvantage (socioeconomic position, perceived social status, and race/ethnicity) interact to promote obesity and insulin resistance is a major goal of our work. A second major goal is characterizing trajectories of vulnerability to the deleterious effects of social disadvantage. Our preliminary studies suggest a major shift in the importance of perceived SES to development of morbidity as an adolescent matures. Understanding when, how and why this shift occurs is necessary to guide development of effective, efficient interventions to decrease health disparities. We use a two-pronged approach to address our goals. First, we extend our large, well established cohort study, The Princeton School District Study, through 2 new waves of data collection. These new data collection efforts, which will occur 3 and 5 years after the last assessment, will re-evaluate the anthropomorphic, psychological, and physiological factors we have collected data on during these first 4 waves of data collection, allowing us to study these youth as they transition to adulthood. Second, we enhance our explanatory model to include psychological traits and two new neuroendocrine mediators of the relationships between social disadvantage and obesity/insulin resistance--tumor necrosis factor-alpha and interleukin-6. Our specific aims are: 1) To characterize the relationship between social disadvantage and inflammatory biomarkers of risk for obesity and Type 2 diabetes from adolescence to early adulthood;2) To characterize the relationships between social disadvantage and psychological factors which may be part of the causal chain linking social disadvantage to obesity/insulin resistance;3) To explore the dynamic interplay between domains of social disadvantage and how these domains interact with putative physiological and psychological paths linking social disadvantage to obesity and insulin resistance. The prospective cohort design allows us to address issues of directionality and reverse causation at a time when rates of obesity and Type 2 diabetes have risen dramatically. This application will provide unique data regarding how disparities in obesity and risk for Type 2 diabetes develop and progress, potentially identifying pathways for social, psychological, and pharmacological intervention. Narrative Elimination of social inequalities in health, including those due to differences in social status, is one of major challenges facing society today. Although disparities due to social status are well documented for heart disease, diabetes, and cancer, as well as many other such chronic diseases which begin early in life but do not become manifest until later in adulthood, the process by which these disparities develop remains a mystery. In order to enhance our understanding of the process by which social inequalities in health accrue, this project proposes to study disparities in obesity and insulin resistance, both of which are precursors for diabetes, heart disease, and cancer, during adolescence and young adulthood.